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Treatment of Primary HIV-1 Infection with Cyclosporin A Coupled with Highly Active Antiretroviral Therapy

Abstract

Primary HIV-1 infection causes extensive immune activation, during which CD4(+) T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4(+) T cell levels, both in terms of percentage and absolute numbers. The increase in CD4(+) T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8(+) or CD4(+) T cell responses. At week 48, the proportion of IFN-gamma-secreting CD4(+) and CD4(+)CCR7(-) T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection.

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References
1.
Chun T, Engel D, Berrey M, Shea T, Corey L, Fauci A . Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci U S A. 1998; 95(15):8869-73. PMC: 21169. DOI: 10.1073/pnas.95.15.8869. View

2.
Bass H, Nishanian P, Hardy W, Mitsuyasu R, Esmail E, Cumberland W . Immune changes in HIV-1 infection: significant correlations and differences in serum markers and lymphoid phenotypic antigens. Clin Immunol Immunopathol. 1992; 64(1):63-70. DOI: 10.1016/0090-1229(92)90060-2. View

3.
Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A . Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999; 401(6754):708-12. DOI: 10.1038/44385. View

4.
Fleury S, de Boer R, Rizzardi G, Wolthers K, Otto S, Welbon C . Limited CD4+ T-cell renewal in early HIV-1 infection: effect of highly active antiretroviral therapy. Nat Med. 1998; 4(7):794-801. DOI: 10.1038/nm0798-794. View

5.
McCune J, Hanley M, Cesar D, Halvorsen R, Hoh R, Schmidt D . Factors influencing T-cell turnover in HIV-1-seropositive patients. J Clin Invest. 2000; 105(5):R1-8. PMC: 377453. DOI: 10.1172/JCI8647. View